Duration Of Postantibiotic Effect Research Articles

Improved N-phenylpyrrolamide inhibitors of DNA gyrase as antibacterial agents for high-priority bacterial strains

In this work, we describe an improved series of N-phenylpyrrolamide inhibitors that exhibit potent activity against DNA gyrase and are highly effective against high-priority gram-positive bacteria. The most potent compounds show low nanomolar IC50 values against Escherichia coli DNA gyrase, and in addition, compound 7c also inhibits E. coli topoisomerase IV in the nanomolar concentration range, making it a promising candidate for the development of potent dual inhibitors for these enzymes. All tested compounds show high selectivity towards the human isoform DNA topoisomerase IIα. Compounds 6a, 6d, 6e and 6f show MIC values between 0.031 and 0.0625 μg/mL against vancomycin-intermediate S. aureus (VISA) and Enterococcus faecalis strains. Compound 6g shows an inhibitory effect against the methicillin-resistant S. aureus strain (MRSA) with a MIC of 0.0625 μg/mL and against the E. faecalis strain with a MIC of 0.125 μg/mL. In a time-kill assay, compound 6d showed a dose-dependent bactericidal effect on the MRSA strain and achieved bactericidal activity at 8 × MIC after 8 h. The duration of the post-antibiotic effect (PAE) on the MRSA strain for compound 6d was 2 h, which corresponds to the PAE duration for ciprofloxacin. The compounds were not cytotoxic at effective concentrations, as determined in an MTS assay on the MCF-7 breast cancer cell line.

In vitro killing of multidrug/extensively drug-resistant Pseudomonas aeruginosa by fosfomycin alone or in combination with antipseudomonal antibiotics

Pseudomonas aeruginosa is a leading cause of nosocomial infections. Given the constant rise in resistance, adequate therapy is increasingly demanding. Fosfomycin recently became an appealing treatment option of bacterial infections due to multidrug-resistant bacteria (MDR). So far, fosfomycin synergy with other antibiotics has been assessed in studies, but only a limited number focused on MDR P. aeruginosa and on the effect of these combinations on the duration of the postantibiotic effect (PAE). We investigated synergy of fosfomycin with an array of antipseudomonal antibiotics using gradient diffusion strip cross method and time-kill method, and their effect on the duration of PAE against 51 variously resistant P. aeruginosa isolates. The highest rate of synergy was observed for combination with ceftazidime (23.4%) and gentamicin (19.1%). The PAE of antibiotic combinations was superior to that of the drugs alone. Our findings indicate that fosfomycin combination therapy may be a valuable treatment alternative.

Bactericidal activities and post-antibiotic effects of ofloxacin and ceftriaxone against drug-resistant Salmonella enterica serovar Typhi.

BackgroundThe clinical response to ceftriaxone in patients with typhoid fever is significantly slower than with ofloxacin, despite infection with Salmonella enterica serovar Typhi (S. Typhi) isolates with similar susceptibilities (MIC 0.03–0.12 mg/L). The response to ofloxacin is slower if the isolate has intermediate susceptibility (MIC 0.25–1.0 mg/L).ObjectivesTo determine the bactericidal activity and post-antibiotic effect (PAE) of ceftriaxone and ofloxacin against S. Typhi.MethodsThe mean time to reach a 99.9% reduction in log10 count (bactericidal activity) and PAE of ceftriaxone and ofloxacin were determined for 18 clinical isolates of S. Typhi in time–kill experiments (MIC range for ofloxacin 0.06–1.0 mg/L and for ceftriaxone 0.03–0.12 mg/L).ResultsThe mean (SD) bactericidal activity of ofloxacin was 33.1 (15.2) min and 384.4 (60) min for ceftriaxone. After a 30 min exposure to ofloxacin, the mean (SD) duration of PAE was 154.7 (52.6) min. There was no detectable PAE after 1 h of exposure to ceftriaxone. For ofloxacin, bactericidal activity and PAE did not significantly differ between isolates with full or intermediate susceptibility provided ofloxacin concentrations were maintained at 4×MIC.ConclusionsInfections with S. Typhi with intermediate ofloxacin susceptibility may respond to doses that maintain ofloxacin concentrations at 4×MIC at the site of infection. The slow bactericidal activity of ceftriaxone and absent PAE may explain the slow clinical response in typhoid.

Is it Worth Combining Solidago virgaurea Extract and Antibiotics against Uropathogenic Escherichia coli rods? An In Vitro Model Study.

European goldenrod (Solidago virgaurea L.) has long been applied in traditional medicine and recommended in the prophylaxis of urinary tract infections (UTIs). However, research describing the antibacterial properties of goldenrod is very limited. Therefore, the aim of the study was to determine the effect of S. virgaurea extract on the survival and biofilm formation of uropathogenic Escherichia coli. The interactions between the goldenrod extract and antibiotics used in UTIs were established. The influence of the extract on the duration of the post-antibiotic effects (PAE) and post-antibiotic sub-MIC effects (PASME) of amikacin and ciprofloxacin were determined. Extract composition was analyzed using coupled UHPLC/MS and the spectrophotometric method. The survival of bacteria was established using the serial dilution assay. The crystal violet assay for biofilm quantification was also used. PAE and PASME were investigated using the viable count method. The obtained results indicate that S. virgaurea extract limits the survival of planktonic forms of bacteria and reduces 24-h biofilm. However, the combination of S. virgaurea extract with antibiotics weakens their antibacterial activity and shortens the duration of PAE and PASME. Therefore, when deciding to use a combination of S. virgaurea extract and amikacin/ciprofloxacin, it is necessary to take into account their antagonistic activity.

Nanobiotic formulations as promising advances for combating MRSA resistance: susceptibilities and post-antibiotic effects of clindamycin, doxycycline, and linezolid.

Antimicrobial activity and post-antibiotic effects (PAEs) are both important parameters in determination of the dosage regimen of antimicrobial agents. In the present study, antimicrobial activity and PAEs of clindamycin, doxycycline, linezolid, and their nanobiotic formulations were evaluated against two methicillin resistant Staphylococcus aureus clinical isolates (MRSA) encoded (MRSA-S1 and MRSA-S2). Nanobiotic formulations increased the susceptibility of MRSA isolates by 4–64 folds as compared to their conventional ones. The PAE values were determined after exposure of MRSA isolates for 1 h to 10× the MICs of the tested antibiotics. The duration of PAEs were recorded after bacterial growth in Mueller Hinton broth (MHB) free from antibiotic has been restored. The PAE values for MRSA-S1 were 2.5 h for the conventional antibiotics. However, the PAEs for nanobiotics were 4 h for both clindamycin and linezolid, while 3 h for doxycycline. For MRSA-S2, linezolid and linezolid nanobiotics PAEs were 3 h. PAEs of clindamycin and clindamycin nanobiotics were 3.75 h and 4 h, respectively. Doxycycline and doxycycline nanobiotics revealed the same PAEs patterns of 3.5 h. The findings of the current study may positively influence the pharmacodynamics of the antibiotics and consequently the dosage regimen of nanobiotics as well as on their clinical outcome.

Pharmacokinetic-pharmacodynamic integration and resistance of tiamulin against Mycoplasma hyopneumoniae in an in vitro dynamic model

Mycoplasma hyopneumoniae is the major pathogen of enzootic pneumonia in pigs. We established an in vitro dynamic model to investigate the relationship between the pharmacokinetic and pharmacodynamic (PK-PD) parameters of tiamulin against M. hyopneumoniae. Static time-killing curves showed that mycoplasmacidal activity (reduced 3.0 log10 (CFU/mL)) was achieved during 48 h when the drug concentration was 8 MIC, and with a maximum kill rate of 0.072/h. In dynamic time-killing studies, only the dose-fractionated regimen achieved mycoplasmacidal activity when drug concentration was 1.44 and 1.92 mg/L. The duration of post antibiotic effect (PAE) at 1 × MIC was 6.27 ± 0.11 h, and prolonged as the concentration of tiamulin increased. The cumulative percentage of time over a 48-h period that the drug concentration exceeds the MIC (%T > MIC) was the best PK-PD parameter to predict the antimicrobial activity of tiamulin against M. hyopneumoniae (R2 = 0.98). Tiamulin showed time-dependent and prolonged PAE activity. Two strains of M. hyopneumoniae (M1, M2) had acquired resistance to tiamulin as well as to valnemulin, tylosin and amikacin. The genome of strain ATCC 25934 was used as a reference for gene-mutation analysis. For strains M1 and M2, a A2058C mutation occurred in domain V of 23S rRNA. These data showed that tiamulin had excellent efficacy and concentration-dependent characteristics against M. hyopneumoniae in vitro. The lower dose was not safe because it could lead to enrichment of resistant bacteria.

Post-antibiotic effect of marbofloxacin, enrofloxacin and amoxicillin against selected respiratory pathogens of pigs

The post-antibiotic effect is defined as the period of bacterial growth suppression that persists after a limited exposure of organisms to antimicrobials and knowledge of its duration is important in establishing and optimising current dosing schedules for the treatment of bacterial infections. The post-antibiotic effect of marbofloxacin, enrofloxacin and amoxicillin were evaluated in vitro for Actinobacillus pleuropneumoniae, Haemophilus parasuis and Pasteurella multocida strains which originated from clinical samples of diseased pigs and were confirmed as susceptible to all tested antimicrobials based on determination of minimal inhibitory concentrations. The post-antibiotic effect for individual antimicrobials was monitored at five and ten times minimum inhibitory concentrations for one and two hours. The duration of the post-antibiotic effect for tested antimicrobials was found to exhibit the following order for all tested pathogens: marbofloxacin > enrofloxacin > amoxicillin. The longest duration of post-antibiotic effect of all tested antimicrobials was found in A. pleuropneumoniae and the shortest post-antibiotic effect duration was detected in P. multocida. No statistical differences in post-antibiotic effect duration were found within marbofloxacin and enrofloxacin in A. pleuropneumoniae and H. parasuis strains. In P. multocida strains there was a statistically significant difference (P = 0.0189). On the other hand, the differences between amoxicillin and marbofloxacin or enrofloxacin were statistically significant in all cases (P-values ranged between 0.0058 and 0.008). The prolonged post-antibiotic effect of fluoroquinolones and amoxicillin on important Gram-negative swine pathogens was confirmed. The results can be used to clarify the effect and mechanism of action of antimicrobial drugs in veterinary medicine.

Invitro synergy and postantibiotic effect of colistin combinations with meropenem and vancomycin against Enterobacteriaceae with multiple carbapenem resistance mechanisms.

The aim of the study was to determine invitro synergy and postantibiotic effect of colistin alone and combined with meropenem or vancomycin against Enterobacteriaceae producing multiple carbapenemases; combinations of two metallo-β-lactamases (MBL) or MBL with OXA-48. Colistin-resistant strain positive for OXA-48 was also included in the study. The antibiotic susceptibility was tested by broth microdilution method. Synergy was tested by chequerboard, time-kill and 2-well method. PAE was determined by viable counting. The chequerboard analysis revealed synergy for colistin combination with meropenem in all isolates with FICI values ranging from 0.12 to 0.24. FICI values for combinations with vancomycin were below 0.5 indicating synergy in two out of four isolates. K.pneumoniae 609815 positive for OXA-48 and colistin resistant showed the most pronounced and consistent synergy effect with meropenem in both chequerboard and time-kill method. Synergy effect in time-kill curves, was observed for K pneumoniae 145846 with two MBLs and colistin resistant K.pneumoniae 609815 positive for OXA-48, with both combinations including meropenem and vancomycin. Colistin alone exhibited short postantibiotic effect (PAE) against all tested isolates. Meropenem markedly prolonged the PAE in two isolates in contrast to vancomycin which did not demonstrate significant effect on the duration of PAE. The synergy effect and the duration of PAE was strain and antibiotic dependent but not related to the resistance gene content.

Postantibiotic effect of colistin alone and combined with vancomycin or meropenem against Acinetobacter spp. with well defined resistance mechanisms

Previous studies found short postantibiotic effect of colistin on Acinetobacter baumannii. Many studies have evaluated the potential for synergy between colistin and other antibiotics against A. baumannii. The aim of this study was to determine in vitro synergy and postantibiotic effect (PAE) of colistin alone and combined with other antibiotics (vancomycin or meropenem) against eight carbapenem-non-susceptible Acinetobacter spp. strains with defined resistance mechanisms. It was hypothesised that vancomycin or meropenem would prologue the PAE of colistin since it was previously found that they exert synergism with colistin in time-kill kinetics and chequerboard analysis. After exposure of 1 hour colistin alone exhibited the negative ( − 0.07 hour) (OXA-143), short (0.2–1.82 hours) (OXA-24, OXA-58, OXA-72, VIM-1+OXA-23, OXA-58+NDM-1, ISAba1/OXA-69) or moderate PAE (3.2 hours) for OXA-23 positive strain. When combined with vancomycin, the PAE was moderate (1.7–4 hours) with OXA-23, OXA-23+VIM-1, OXA-72 and OXA-24 positive strains while with OXA-58, OXA-143, OXA-58/NDM-1 and ISAba1/OXA-69 positive strains, it was not possible to calculate mean duration of PAE because there was no regrowth after exposure to antibiotics or it was longer than 5 hours. The combination with meropenem resulted in short (0.2 hours) (OXA-143), moderate (2.4–3.73 hours) (OXA-24, OXA-58, OXA-23, OXA-23+VIM-1), long PAE of 5 hours (OXA-23) or longer than 5 hours (OXA-58+VIM-1, ISAba1/OXA-69). From the clinical point of view, the prolongation of colistin PAE when combined with other antibiotics could provide a rationale for the modification of the dosing interval and could be important for the optimization of the treatment regimen and the minimization of drug-induced side effects.

Pterostilbene Reduced Post-Antibiotic Effect Time of Linezolid against Methicillin-Resistant Staphylococcus aureus

Pterostilbene is biologically classified as a phytoalexin, which is part of the plant's defense system in response to pathogen infection. The present study is to identify the type of interaction and post-antibiotic effect time of pterostilbene in combination with linezolid against methicillin-resistant Staphylococcus aureus American type culture collection 43300 and methicillin-resistant S. aureus American type culture collection 33591. The minimum inhibitory concentration values of individual antimicrobial agents were determined using microbroth dilution technique whereas the microdilution checker board assay was employed to verify the type of interaction of the combined agents from the fractional inhibitory concentration index values. The post-antibiotic effect time of pterostilbene and linezolid and in combination treatment was evaluated using viable plate count method. The minimum inhibitory concentration value of pterostilbene against both strains were the same (31.25 μg/ml) compared to linezolid at 0.78 μg/ml and 1.56 μg/ml, against 43300 and 33591 strain, respectively. microdilution checker analysis of pterostilbene in combination with linezolid against both methicillin-resistant S. aureus strains displayed fractional inhibitory concentration value of 1.25. Despite the indifference interaction between pterostilbene and linezolid as shown by microdilution checker study, post-antibiotic effect analysis demonstrated antagonism as depicted by a decrease of post-antibiotic effect time of linezolid by pterostilbene against both methicillin-resistant S. aureus strains. The duration of post-antibiotic effect time obtained for pterostilbene were twice (3.6±0.15 h) that of linezolid (1.8±0.31 h) against methicillin-resistant S. aureus American type culture collection 43300. However, pterostilbene exhibited shorter post-antibiotic effect time of 0.3±0.10 h compared to linezolid (0.9±0.06 h) against 33591 strain. In conclusion, pterostilbene was not able to prolong the post-antibiotic effect duration of linezolid in both strains and each of the antimicrobials demonstrated a more favorable timing of doses when these agents were used singly.

Effects of various antibiotics alone or in combination with doripenem against Klebsiella pneumoniae strains isolated in an intensive care unit.

Colistin, tigecycline, levofloxacin, tobramycin, and rifampin alone and in combination with doripenem were investigated for their in vitro activities and postantibiotic effects (PAEs) on Klebsiella pneumoniae. The in vitro activities of tested antibiotics in combination with doripenem were determined using a microbroth checkerboard technique. To determine the PAEs, K. pneumoniae strains in the logarithmic phase of growth were exposed for 1 h to antibiotics, alone and in combination. Recovery periods of test cultures were evaluated using viable counting after centrifugation. Colistin, tobramycin, and levofloxacin produced strong PAEs ranging from 2.71 to 4.23 h, from 1.31 to 3.82 h, and from 1.35 to 4.72, respectively, in a concentration-dependent manner. Tigecycline and rifampin displayed modest PAEs ranging from 1.18 h to 1.55 h and 0.92 to 1.19, respectively. Because it is a beta-lactam, PAEs were not exactly induced by doripenem (ranging from 0.10 to 0.18 h). In combination, doripenem scarcely changed the duration of PAE of each tested antibiotic alone. The findings of this study may have important implications for the timing of doses during K. pneumoniae therapy with tested antibiotics.

Post-antibiotic and post-antibiotic sub-MIC effects of gentamicin, sophoraflavanone G, and their combination against a clinical isolate of Staphylococcus aureus

Abstract Background: Post-antibiotic effect (PAE) defines the potential of a drug to delay re-growth of a bacterial population after short-term exposure and removal of a drug. Determination of the PAE is recommended in preclinical evaluation of all new antimicrobial agents, because it influences optimal antimicrobial dosing intervals. Objective: Evaluate the PAE and PA-SME of gentamicin and sophoraflavanone G against Staphylococcus aureus (S. aureus) itself and in combination. Methods: A spectrophotometric method was used to determine the PAE and PA-SME. Results: Sophoraflavanone G and gentamicin, showed considerable PAE and PA-SME at the tested concentrations against S. aureus. The increased duration of PAE caused by sophoraflavanone G and gentamicin was dosedependent. In addition, sophoraflavanone G at sub-MIC concentrations enhanced the PAE and PA-SME of gentamicin in a dose-dependent manner. The highest enhancing effect was observed for gentamicin at the synergistic MIC and 1/2 the synergistic MIC levels against S. aureus 0.03 μg/mL (30 ng/mL) of sophoraflavanone G (with PAE=55 minutes). It enhanced the post-antibiotic sub-MIC effect (PA-SME) duration of gentamicin at concentrations of 4 μg/mL from 15 minutes to 80 minutes (a six-fold increase). Conclusion: Sophoraflavanone G is promising for the preparation of an effective therapeutic formulation against gentamicin-resistant S. aureus.

Minimum Inhibitory Concentration and Postantibiotic Effect of Amikacin for Equine Isolates of Methicillin‐Resistant Staphylococcus aureus In Vitro

To report the minimum inhibitory concentration (MIC) of amikacin sulfate for equine clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and characterize the initial kill and duration of the postantibiotic effect (PAE) for selected strains. Experimental study. Isolates of MRSA (n=35) had their amikacin MIC determined using the E-test agar diffusion method. Two isolates with MICs>256 microg/mL limit were further characterized using broth macrodilution. Six distinct isolates with amikacin MICs of 32, 48, 128 (2 isolates) and 500 (2 isolates) microg/mL had PAE determinations made over a range of amikacin concentrations from 31.25-1000 microg/mL using standard culture-based techniques. Median MIC of the 35 isolates was 32 microg/mL (range 2 to >256 microg/mL). Mean PAE of selected MRSA strains had an overall mean (all amikacin doses) of 3.43 hours (range 0.10-9.57 hours). PAE for MRSA exposed to amikacin at 1000 microg/mL was 6.18 hours (range 3.30-9.57 hours), significantly longer than that for all other concentrations (P<.0001). There was no statistically significant effect of isolate MIC on PAE. Isolates had a wide range of MIC; however, growth of all 6 selected strains were inhibited within the range of concentrations tested, including 2 strains with MICs of 500 microg/mL. PAE duration was not influenced by the MIC of amikacin but was significantly longer with treatment at 1000 microg/mL than at lower concentrations. Clinical isolates of MRSA are susceptible to amikacin at concentrations achieved by regional perfusion: however, the modest duration of PAE observed suggest that further laboratory and in vivo evaluation be conducted before recommending the technique for clinical use.

Postantibiotic and Post-Beta-Lactamase Inhibitor Effect of Carbapenems Combined with EDTA against Pseudomonas aeruginosa Strains Producing VIM-Metallo Beta-Lactamases

Background and Aim: Postantibiotic effect (PAE) is a delay of bacterial growth after short exposure to antibiotics. The phenomenon of continuing suppression of bacterial growth after removal of β-lactamase inhibitors is termed post-β-lactamase inhibitor effect (PLIE). Recently, Pseudomonas aeruginosa strains producing metallo-β-lactamases were described in many countries of the world. The aim of the study was to investigate the PLIE of carbapenems in combinations with EDTA against VIM-MBL-positive strains of P. aeruginosa. Methods: The experiments were performed on two Pseudomonas aeruginosa isolates, one producing VIM-1 and the other producing VIM-2 metallo-β-lactamase. Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBC) of imipenem and meropenem alone and combined with EDTA, time-kill curves, PAE and PLIE were performed as described previously. Results: The duration of PAE with meropenem combined with EDTA at 8 × MIC was longer against both VIM-1 and VIM-2 producer than that of imipenem with EDTA on VIM-1- and VIM-2-positive strains. The duration of PLIE was similar on both strains of P. aeruginosa regardless of the sort of carbapenem. At lower concentrations, meropenem with EDTA induced slightly longer PAE and PLIE than imipenem with EDTA. Conclusions: This study has shown that EDTA combined with carbapenems produced a significant PLIE on VIM-MBL-positive P. aeruginosa strains. The results do not have any clinical relevance so far since metal chelators such as EDTA are not used as therapeutic agents due to their toxicity.

Concentration-Dependent Mycobacterium tuberculosis Killing and Prevention of Resistance by Rifampin

Rifampin is a cornerstone of modern antituberculosis therapy. However, rifampin's half-life of 3 h is believed to limit its utility for intermittent therapy, so new congeners with long half-lives are being developed. Using an in vitro pharmacokinetic-pharmacodynamic model of tuberculosis, we examined the relationships between rifampin exposure, microbial killing of log-phase-growth Mycobacterium tuberculosis, and suppression of resistance. Rifampin's microbial killing was linked to the area under the concentration-time curve-to-MIC ratio. The suppression of resistance was associated with the free peak concentration (C(max))-to-MIC ratio and not the duration that the rifampin concentration was above MIC. Rifampin prevented resistance to itself at a free C(max)/MIC ratio of > or =175. The postantibiotic effect duration was > or =5.2 days and was most closely related to the C(max)/MIC ratio (r(2) = 0.96). To explain rifampin's concentration-dependent effect, we examined the kinetics of rifampin entry into M. tuberculosis. Rifampin achieved concentration-dependent intracellular steady-state concentrations within 15 min. Our results suggest that doses of rifampin higher than those currently employed would optimize the effect of rifampin, if patients could tolerate them. Another major implication is that in the design of new rifampin congeners for intermittent therapy, the important properties may include (i) the efficient entry of the rifamycin into M. tuberculosis, (ii) the achievement of a free C(max)/MIC of >175 that can be tolerated by patients, and (iii) a long postantibiotic effect duration.

Antisense PNA Accumulates in Escherichia coli and Mediates a Long Post-antibiotic Effect

Antisense agents that target growth-essential genes display surprisingly potent bactericidal properties. In particular, peptide nucleic acid (PNA) and phosphorodiamidate morpholino oligomers linked to cationic carrier peptides are effective in time kill assays and as inhibitors of bacterial peritonitis in mice. It is unclear how these relatively large antimicrobials overcome stringent bacterial barriers and mediate killing. Here we determined the transit kinetics of peptide-PNAs and observed an accumulation of cell-associated PNA in Escherichia coli and slow efflux. An inhibitor of drug efflux pumps did not alter peptide-PNA potency, indicating a lack of active efflux from cells. Consistent with cell retention, the post-antibiotic effect (PAE) of the anti-acyl carrier protein (acpP) peptide-PNA was greater than 11 hours. Bacterial cell accumulation and a long PAE are properties of significant interest for antimicrobial development.

Clinical issues surrounding once-daily aminoglycoside dosing in children.

Aminoglycoside antibiotics are first-line treatment for many infectious diseases in the pediatric population and are effective in adults. The traditional dosing interval in children is every 8-12 hours. Studies in adults reported equivalent efficacy and equal or less toxicity with once-daily regimens. Despite many studies in the adult population, this approach has yet to become standard practice in most pediatric hospitals. Reasons for lack of acceptance of this strategy in children include rapid aminoglycoside clearance, unknown duration of postantibiotic effect, safety concerns, and limited clinical and efficacy data.

Aminoglycoside antibiotics and post-antibiotic effects

Man has been fighting diseases for centuries. One of the major battles is against microorganisms and diseases they cause. A health education course was organized on prescribing aminoglycoside antibiotics and postantibiotic effect. The aim of the course was to change the prescription habits in our colleagues. The postantibiotic effect of aminoglycoside antibiotics as well as impact of subinhibiting doses on duration of postantibiotic effect requires modification of previous therapeutic protocols. Single daily dose has the same or even greater effect than multiple daily doses. The toxicity of aminoglycosides is not increased and remains the same or smaller in single daily regimens. The single daily dose regimen of aminoglycosides has been used in 63.6% of cases in Clinic for Infectious Diseases of the Clinical Center of Novi Sad, 41.2% in Outpatient Health Care Center of Novi Sad "Liman" and this regimen has not been used in General Practice Department, Children's Health Care Department and Ear, Nose and Throat Clinic at all. The twice daily regimen has been used instead. Doctors are aware of the postantibiotic effect, but vast majority are still bound to their old habits in regard to prescribing antibiotics. Our educational course failed to achieve its goal.

Postantibiotic effects and postantibiotic sub-MIC effects of erythromycin, roxithromycin, tilmicosin, and tylosin on Pasteurella multocida

When intermittent dosing is used during treatment, the concentrations of antibiotics fluctuate and subinhibitory concentrations may occur between doses. Postantibiotic effects (PAEs) and postantibiotic subinhibitory effects (PA SMEs) on bacteria may provide additional, valuable information for the rational use of a drug in clinical practice. In this study tilmicosin was the most active antibiotic tested against P. multocida type D with MICs ranging from 4–16 mg/l. Roxithromycin and tilmicosin induced a statistically significantly longer PAE than did tylosin against P. multocida types A and D ( P<0.05). The duration of PAEs and PA SMEs were proportional to the concentrations of drugs used for exposure. The PA SMEs were substantially longer than PAEs on P. multocida. Tilmicosin had a longer PA SME compared with erythromycin, roxithromycin and tylosin for P. multocida. The computerized incubator used in the present study provided an efficient and convenient determination of PAE and PA SME, allowing frequent measurements of the bacterial growth.

Activity and postantibiotic effect of marbofloxacin, enrofloxacin, difloxacin and ciprofloxacin against feline Bordetella bronchiseptica isolates

The minimum inhibitory concentration (MIC) and postantibiotic effect (PAE) of marbofloxacin, enrofloxacin, difloxacin and ciprofloxacin were evaluated in vitro against 43 feline-source Bordetella bronchiseptica strains. All strains tested were susceptible to marbofloxacin and enrofloxacin (MIC90 0.5 mg/l), while 93 and 84% of the strains were susceptible, respectively, to ciprofloxacin and difloxacin with MIC 90 values of, respectively, 1 and 8 mg/l. The PAE was studied in 10 strains by exposure of bacteria to marbofloxacin, enrofloxacin, difloxacin and ciprofloxacin at 5 and 10 times minimum inhibitory concentration (MIC) for 1 and 2 h. Regrowth was determined by measuring the viable counts after drug removal by a 10 3 dilution procedure. PAEs increased as a function of concentration and exposure time. The mean duration of PAEs varied between 1.1 and 8.2 h, showing the following order: marbofloxacin>enrofloxacin>ciprofloxacin>difloxacin. These data are encouraging since fluoroquinolones have a possible role in the clinical treatment of B. bronchiseptica infections, and the strong PAE caused by quinolones may contribute to the in vivo efficacy of these drugs.